SKAP1 Gene - Src Kinase Associated Phosphoprotein 1 | Function, Mutations & Disease

SKAP1 (Src kinase associated phosphoprotein 1) encodes an adaptor protein that functions downstream of T-cell receptor (TCR) activation. It contains a pleckstrin homology (PH) domain and a Src homology 3 (SH3) domain, mediating interactions with signaling molecules such as FYN, LCP2, and ADAP. SKAP1 is essential for integrin activation, cytoskeletal rearrangement, and immune synapse formation in T cells.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T-cell receptor signaling pathway (KEGG: hsa04660)

• Integrin signaling pathway (Reactome: R-HSA-354192)

• Adaptor protein interactions in T-cell activation (Reactome: R-HSA-202430)

SKAP1 (SKAP55) is a 359-amino-acid adaptor protein predominantly expressed in T cells and lymphoid tissues. It contains an N-terminal PH domain that binds phosphatidylinositol lipids, a central SH3 domain that interacts with proline-rich motifs of partners like ADAP and FYN, and a C-terminal region involved in membrane localization. SKAP1 is phosphorylated upon TCR engagement and recruits signaling complexes to the immune synapse, regulating integrin activation (e.g., LFA-1) and T-cell adhesion. Loss of SKAP1 leads to defective T-cell activation and impaired immune responses.